A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction
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A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction. / Jabbari, Reza; Glinge, Charlotte; Jabbari, Javad; Risgaard, Bjarke; Winkel, Bo Gregers; Terkelsen, Christian Juhl; Tilsted, Hans-Henrik; Jensen, Lisette Okkels; Hougaard, Mikkel; Haunsø, Stig; Engstrøm, Thomas; Albert, Christine M; Tfelt-Hansen, Jacob.
In: PLOS ONE, Vol. 12, No. 1, e0170193, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction
AU - Jabbari, Reza
AU - Glinge, Charlotte
AU - Jabbari, Javad
AU - Risgaard, Bjarke
AU - Winkel, Bo Gregers
AU - Terkelsen, Christian Juhl
AU - Tilsted, Hans-Henrik
AU - Jensen, Lisette Okkels
AU - Hougaard, Mikkel
AU - Haunsø, Stig
AU - Engstrøm, Thomas
AU - Albert, Christine M
AU - Tfelt-Hansen, Jacob
PY - 2017
Y1 - 2017
N2 - BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.
AB - BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.
KW - Aged
KW - Case-Control Studies
KW - Denmark
KW - Female
KW - Genotype
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Infarction
KW - NAV1.5 Voltage-Gated Sodium Channel
KW - Polymorphism, Single Nucleotide
KW - Ventricular Fibrillation
KW - Journal Article
U2 - 10.1371/journal.pone.0170193
DO - 10.1371/journal.pone.0170193
M3 - Journal article
C2 - 28085969
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e0170193
ER -
ID: 186525460